Hydrochloric Acid → HCID 51346867, compound

HRID 887165Notes

Reaction equation

HRID 887165 reaction equation
[Si](O[C@@:9]1([CH2:49][C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)[CH2:13][CH2:12][CH:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([NH:21][S:22]([C:25]3[CH:30]=[CH:29][C:28]([C:31]4[S:32][CH:33]=[C:34]([C:36]5[CH:41]=[CH:40][C:39]([C:42]([F:45])([F:44])[F:43])=[CH:38][CH:37]=5)[N:35]=4)=[CH:27][CH:26]=3)(=[O:24])=[O:23])=[CH:17][CH:16]=2)[N:10]1C([O-])=O)(C(C)(C)C)(C)C.Cl.C[OH:58]>>[OH:58][C@H:49]([C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)[C@@H:9]1[NH:10][C@H:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([NH:21][S:22]([C:25]3[CH:30]=[CH:29][C:28]([C:31]4[S:32][CH:33]=[C:34]([C:36]5[CH:37]=[CH:38][C:39]([C:42]([F:43])([F:45])[F:44])=[CH:40][CH:41]=5)[N:35]=4)=[CH:27][CH:26]=3)(=[O:23])=[O:24])=[CH:17][CH:16]=2)[CH2:12][CH2:13]1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 887MethanolHCID 86634923HCID 86634923, compound

Product 1

HCID 51346867HCID 51346867, compoundYield 61%

Procedure

To a solution of 16 mg (0.02 mmol) of tert-butyl (2R,5S)-2-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl-5-(4-{[(4-{4-[4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl}phenyl)sulfonyl]amino}benzyl)pyrrolidine-1-carboxylate (from Step A) in 0.25 mL methanol was added 0.25 mL conc. HCl and the reaction mixture stirred at room temperature for 30 min. Azeotrop with toluene (2×) to remove water. The residue was taken up in acetonitrile/water/MeOH (9:1:1) and purified on the Gilson HPLC eluting with a 0-50% gradient of acetonitrile/water with 0.05% TFA buffer. The fractions containing the product were combined, frozen, and lyophilized to give a white foam (7.3 mg, 61%). mlz (ES) 650 (MH)+. 1HNMR (500 MHz, CD3OD) δ: 8.22 (br d, J=7.8 Hz, 2H), 8.15-8.10 (m, 3H), 7.86 (d, J=7.8 Hz, 2H), 7.72 (d, J=7.8 Hz, 2H), 7.38-7.30 (m, 4H), 7.16 (br d, J=7.8 Hz, 2H), 7.09 (br d, J=7.8 Hz, 2H), 4.56 (d, J=8.1 Hz, 1H), 3.54-3.45 (m, 2H), 2.93 (dd, J=6.4, 13.0 Hz, 1H), 2.82 (dd, J=7.7, 13.0 Hz, 1H), 1.90-1.82 (m, 1H), 1.68-1.53 (m, 3H).

Workup

  1. customAzeotrop with toluene (2×) to remove water
  2. custompurified on the Gilson HPLC
  3. washeluting with a 0-50% gradient of acetonitrile/water with 0.05% TFA buffer
  4. additionThe fractions containing the product
  5. temperaturefrozen

Sources & evidence

ORD record
ord-007b628d61d34f33accdc20dca7884c9
Source dataset
uspto-grants-2012_08
Patent number
US08247415B2

Reaction notes

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